Kozich, Viktor ORCID: 0000-0001-5820-5277, Schwahn, Bernd C., Sokolova, Jitka, Krizkova, Michaela, Ditroi, Tamas, Krijt, Jakub ORCID: 0000-0002-1738-654X, Khalil, Youssef ORCID: 0000-0001-9025-3017, Krizek, Tomas, Vaculikova-Fantlova, Tereza, Stiburkova, Blanka, Mills, Philippa, Clayton, Peter, Barvikova, Kristyna, Blessing, Holger, Sykut-Cegielska, Jolanta, Dionisi-Vici, Carlo, Gasperini, Serena, Garcia-Cazorla, Angeles, Haack, Tobias B., Honzik, Tomas, Jesina, Pavel, Kuster, Alice, Laugwitz, Lucia, Martinelli, Diego, Porta, Francesco, Santer, Rene, Schwarz, Guenter and Nagy, Peter (2022). Human ultrarare genetic disorders of sulfur metabolism demonstrate redundancies in H2S homeostasis. Redox Biol., 58. AMSTERDAM: ELSEVIER. ISSN 2213-2317

Full text not available from this repository.

Abstract

Regulation of H2S homeostasis in humans is poorly understood. Therefore, we assessed the importance of in-dividual enzymes in synthesis and catabolism of H2S by studying patients with respective genetic defects. We analyzed sulfur compounds (including bioavailable sulfide) in 37 untreated or insufficiently treated patients with seven ultrarare enzyme deficiencies and compared them to 63 controls. Surprisingly, we observed that patients with severe deficiency in cystathionine beta-synthase (CBS) or cystathionine gamma-lyase (CSE) -the enzymes primarily responsible for H2S synthesis -exhibited increased and normal levels of bioavailable sulfide, respectively. However, an approximately 21-fold increase of urinary homolanthionine in CBS deficiency strongly suggests that lacking CBS activity is compensated for by an increase in CSE-dependent H2S synthesis from accumulating ho-mocysteine, which suggests a control of H2S homeostasis in vivo. In deficiency of sulfide:quinone oxidoreductase -the first enzyme in mitochondrial H2S oxidation -we found normal H2S concentrations in a symptomatic patient and his asymptomatic sibling, and elevated levels in an asymptomatic sibling, challenging the requirement for this enzyme in catabolizing H2S under physiological conditions. Patients with ethylmalonic encephalopathy and sulfite oxidase/molybdenum cofactor deficiencies exhibited massive accumulation of thiosulfate and sulfite with formation of large amounts of S-sulfocysteine and S-sulfohomocysteine, increased renal losses of sulfur com-pounds and concomitant strong reduction in plasma total cysteine. Our results demonstrate the value of a comprehensive assessment of sulfur compounds in severe disorders of homocysteine/cysteine metabolism and provide evidence for redundancy and compensatory mechanisms in the maintenance of H2S homeostasis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kozich, ViktorUNSPECIFIEDorcid.org/0000-0001-5820-5277UNSPECIFIED
Schwahn, Bernd C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sokolova, JitkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krizkova, MichaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ditroi, TamasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krijt, JakubUNSPECIFIEDorcid.org/0000-0002-1738-654XUNSPECIFIED
Khalil, YoussefUNSPECIFIEDorcid.org/0000-0001-9025-3017UNSPECIFIED
Krizek, TomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vaculikova-Fantlova, TerezaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stiburkova, BlankaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mills, PhilippaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clayton, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barvikova, KristynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blessing, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sykut-Cegielska, JolantaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dionisi-Vici, CarloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gasperini, SerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Cazorla, AngelesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haack, Tobias B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Honzik, TomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jesina, PavelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuster, AliceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laugwitz, LuciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinelli, DiegoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Porta, FrancescoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Santer, ReneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarz, GuenterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nagy, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-696460
DOI: 10.1016/j.redox.2022.102517
Journal or Publication Title: Redox Biol.
Volume: 58
Date: 2022
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 2213-2317
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CYSTATHIONINE BETA-SYNTHASE; MOLYBDENUM COFACTOR DEFICIENCY; HYDROGEN-SULFIDE; PLASMA HOMOCYSTEINE; ETHYLMALONIC ENCEPHALOPATHY; PROTEIN-BINDING; REDOX STATUS; AMINO-ACIDS; MICE; CYSTEINEMultiple languages
Biochemistry & Molecular BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69646

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item